Buspirone pharmacokinetics

Pharmacokinetics Buspirone is rapidly absorbed and undergoes extensive first-pass metabolism. Approximately 95% of buspirone is plasma protein bound. In a single dose study, 29% to 63% of the dose was excreted in the urine within 24 hours. 

B.4.2.2 Nonbenzodlazeptnes GG-NPD was used by Kivisto et al. (1999) to quantitate the nonbenzodiazepine anxiolytic buspirone and its major metabolite, l-(2-pyrimidinyl)-piperazine, using separate extraction methods and separate assays. The hmit of quantification in plasma for both compounds was 0.2 ng/mL, which makes this assay useful for pharmacokinetic studies of this compound (Kivisto et al., 1999). A rapid, simple method for analysis of buspirone in rat brain requiring a single extraction step followed by GC-NPD has also been described (Lai. et al., 1997). 

Of the non-benzodiazepines that have been introduced recently for the treatment of anxiety and insomnia, buspirone and zopiclone have been the most extensively investigated so far. The pharmacokinetic characteristics of... 

In the treatment of children and adolescents with anxiety disorders clinicians have a wide variety of pharmacologic options beyond the antidepressants (Shader and Greenblatt, 1995 Lydiard et ah, 1996 Riddle et ah, 1999). The benzodiazepines (BZs), with their favorable safety profile and quick onset of action, are attractive alternatives for the treatment of acute anxiety. While the clinical effectiveness of buspirone has not been proven in children, buspirone is used alone or in combination with other drugs in the treatment of anxiety disorders. The antihistamines are often used to treat insomnia and may reduce acute mild agitation. Zolpidem (Ambien) is occasionally used for its sedative properties. This chapter reviews the structure, proposed mechanisms of action, pharmacodynamic principles, and pharmacokinetic principles of these drugs. 

Mahmood, I. and Sahajwalla, C. (1999) Clinical pharmacokinetics and pharmacodynamics of buspirone, an anxiolytic drug. Clin Pharmacokinet 36 277-2 7. 

Mayol, R.F., Adamson, D.S., Gammans, R.E., and LaBudde, J.A. (1985) Pharmacokinetics and disposition of 14C-buspirone HCl after intravenous and oral dosing in man. Clin Pharmacol Ther... 

Sakr, A. and Andheria, M. (2001) A comparative multidose pharmacokinetic study of buspirone extended-release tablets with a reference immediate-release product. / Clin Pharmacol 41 886-894. 

Tigel, RD., Uderman, H.D., Shiovitz, T.M., Sramek, J.J., and Cutler, N.R. (2001) Pharmacokinetics and tolerability of buspirone during oral administration to children and adolescents with anxiety disorder and normal healthy adults. / Clin Pharmacol 41 1351-1358. 

As of the date of this chapter (circa March, 2002), labeling changes regarding pediatric use have resulted from only two programs—the study of buspirone in pediatric GAD and a pharmacokinetic study of fluvoxamine in pediatric OCD (fluvoxamine already had a controlled clinical trial in pediatric patients). Two placebo-controlled trials with buspirone in pediatric GAD did not reveal a treatment effect, and this negative outcome is reflected in Buspar labeling. A pharmacokinetic study of fluvoxamine dosed at 100 mg bid in pediatric... 

No pharmacokinetic, dose-finding, controlled efficacy, or safety studies of buspirone in children or adolescents have been conducted. Although b -blockers have been used to treat anxiety and aggressive dyscontrol in children and adolescents, no controlled studies and no pharmacokinetic data exist. 

Buspirone tends to be used preferentially in patients with chronic and persistent anxiety, in patients with comorbid substance abuse, and in elderly patients, because it is well tolerated and has no significant pharmacokinetic drug interactions. What is clear is that buspirone shows reproducible efficacy in certain animal models of anxiety and in GAD, which points to a potentially important role of serotonin in mediating anxiety symptoms through 5HT1A receptors. Buspirone also has a role as an augmenting agent for the treatment of resistant depression, as discussed in Chapter 7. 

Lamberg TS, Kivisto KT, Neuvonen PJ. Lack of effect of terfenadine on the pharmacokinetics of the CYP3A4 substrate buspirone. Pharmacol Toxicol 1999 84 165-169. 

The model described above has been successfully applied to characterize the in vivo concentration effect relationships of several 5-HT1A agonists including flesinoxan and buspirone [558,559]. This model has also linked with the operational model of agonism into a full mechanism-based pharmacokinetic-dynamic model [560]. 

The effects of fluvoxamine on the pharmacokinetics and pharmacodynamics of buspirone have been investigated in 10 healthy volunteers. Fluvoxamine moderately increased plasma buspirone concentrations and reduced the production of the active metabolite of buspirone. The mechanism of this interaction is probably inhibition of CYP3A4. However, this pharmacokinetic interaction was not associated with impaired psychomotor performance and is probably of limited clinical significance (33). 

Neuvonen PJ. The effect of fluvoxamine on the pharmacokinetics and pharmacodynamics of buspirone. Eur J Clin Pharmacol 1998 54(9-10) 761-6. 

In a randomized, two-phase crossover study, the effects of grapefruit juice on the pharmacokinetics and pharmacodynamics of oral buspirone were investigated in 10 healthy volunteers. Grapefruit juice increased the mean peak plasma concentration of buspirone 4.3-fold (26). Large amounts of grapefruit juice should be avoided in patients taking buspirone. 

The effects of rifampicin on the pharmacokinetics and pharmacodynamics of buspirone were investigated in 10 young healthy volunteers. There was a significant reduction in the effects of buspirone in three of the six psychomotor tests used after rifampicin pretreatment. The interaction between rifampicin and buspirone is probably mostly due to increased CYP3A4 activity. Buspirone will most likely have a greatly reduced anxiolytic effect when it is used together with rifampicin or other potent inducers of CYP3A4, such as phenytoin and carbamazepine... 

Sakr A, Andheria M. Pharmacokinetics of buspirone extended-release tablets a single-dose study. J Clin Pharmacol 2001 41(7) 783-9. 

Ten healthy volunteers took oral terfenadine 120 mg/day for 3 days and then took buspirone 10 mg terfenadine had no significant effects on the pharmacokinetics of buspirone (9). 

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